Article
Cell Biology
Cansu Gorgun, Chiara Africano, Maria Chiara Ciferri, Nadia Bertola, Daniele Reverberi, Rodolfo Quarto, Silvia Ravera, Roberta Tasso
Summary: This study demonstrates that EVs derived from MSCs preconditioned with hypoxia inflammatory cytokines can attenuate inflammaging and alleviate age-related inflammation and mitochondrial dysfunction.
Review
Biochemistry & Molecular Biology
Gyuzyal Tabeeva, Denis Silachev, Polina Vishnyakova, Alexandra Asaturova, Timur Fatkhudinov, Antonina Smetnik, Madina Dumanovskaya
Summary: Disruption of endometrial regeneration, fibrosis formation, and intrauterine adhesions are common causes of thin endometrium and/or Asherman's syndrome, leading to infertility and adverse obstetric outcomes. Current methods do not restore the regenerative properties of the endometrium. Cell therapy using MMSCs has shown promising results in tissue damage repair, particularly through paracrine effects of EVs secreted by MMSCs, which stimulate progenitor cells and exert cytoprotective, antiapoptotic, and angiogenic effects. This review provides information on the regulatory mechanisms of endometrial regeneration, associated pathological conditions, and the role of MMSCs and EVs in endometrial repair and reproductive processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ying Zhu, Zhao-Fu Liao, Miao-Hua Mo, Xing-Dong Xiong
Summary: Extracellular vesicles (EVs), including mesenchymal stromal cell-derived EVs (MSC-EVs), play crucial roles in cell-cell communication and have potential therapeutic applications in various vascular disorders. MSC-EVs have shown beneficial effects on angiogenesis and different vasculopathies such as atherosclerosis and vascular restenosis. Moreover, modified MSC-EVs and suitable biomaterials can further enhance their therapeutic effects. This review provides an overview of the functional roles of MSC-EVs in maintaining vascular homeostasis and discusses strategies to optimize their therapeutic applications.
Article
Biochemistry & Molecular Biology
Svetlana Demyanenko, Maria A. Pitinova, Yulia N. Kalyuzhnaya, Andrey M. Khaitin, Svetlana A. Batalshchikova, Natalya M. Dobaeva, Yulia A. Shevtsova, Kirill Goryunov, Egor Y. Plotnikov, Svetlana G. Pashkevich, Gennady T. Sukhikh, Denis N. Silachev
Summary: Peripheral nerve injury is a significant medical problem without effective treatment currently. However, the use of multipotent mesenchymal cells (MSCs)-derived extracellular vesicles (EVs) shows promise in promoting the regeneration of peripheral nerves after injury. In a rat model of sciatic nerve injury, the application of MSCs-EVs gel significantly reduced muscle atrophy and improved functional recovery. The results suggest that this therapeutic approach may be efficient for the treatment of acute peripheral nervous system injuries.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
J. Vos, H. Tejeda-Mora, A. Merino, L. Wu, W. W. Woud, J. A. A. Demmers, W. F. J. van IJcken, M. E. J. Reinders, M. J. Hoogduijn
Summary: This study examines the bio-distribution and longevity of membrane particles (MP) derived from human mesenchymal stromal cells (MSC) after intravenous administration in mice. It is found that MP mainly distribute in plasma and leukocytes, remaining in circulation for up to 24 hours, and impact liver function inducing metabolic pathways.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Cell & Tissue Engineering
Ahmed Lotfy, Noha M. AboQuella, Hongjun Wang
Summary: Mesenchymal stromal/stem cells (MSCs) are widely used in cell therapy due to their immunomodulatory and regenerative properties. The production of various factors via extracellular vesicles, especially exosomes, governs the efficacy of MSCs. MSC-derived exosomes (MSC-Exos) show advantages over MSCs themselves by reducing adverse effects. Clinical studies are assessing the therapeutic effect of MSC-Exos in different diseases, and production methods, dosage, and administration routes are being explored.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Elia Bari, Ilaria Roato, Giuseppe Perale, Filippo Rossi, Tullio Genova, Federico Mussano, Riccardo Ferracini, Marzio Sorlini, Maria Luisa Torre, Sara Perteghella
Summary: A new strategy was developed to improve the osteoinductivity of SmartBone (SB) by loading the SB scaffolds with freeze-dried formulation of mesenchymal stem cell (MSC)-secretome. The study showed that SBlyo significantly enhanced cell proliferation and tissue formation compared to SB, suggesting a more effective bone formation induction by SBlyo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biotechnology & Applied Microbiology
Martina Sandona, Lorena Di Pietro, Federica Esposito, Alessia Ventura, Antonietta Rosa Silini, Ornella Parolini, Valentina Saccone
Summary: Mesenchymal stromal cells (MSCs) are multipotent cells found in various tissues that have anti-fibrotic and immunoregulatory properties. Their secretome, including extracellular vesicles (EVs), can mimic the therapeutic effects of MSCs and offer advantages such as easier storage and safer administration for muscle regeneration in different diseases.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Veterinary Sciences
Manon Jammes, Romain Contentin, Frederic Casse, Philippe Galera
Summary: Osteoarthritis is a degenerative disease without a curative treatment. Studying equine OA can help improve horse health and serve as preclinical studies for human medicine. The immunomodulatory and regenerative potentials of mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) offer promising acellular therapy options. Optimizing MSC secretome potential and exploring pro-inflammatory environments could enhance MSC therapies for managing OA.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Stephen Lenzini, Koushik Debnath, Jagdish C. Joshi, Sing Wan Wong, Kriti Srivastava, Xue Geng, Ik Sung Cho, Angela Song, Raymond Bargi, James C. Lee, Gary C. H. Mo, Dolly Mehta, Jae-Won Shin
Summary: Recent research showed that seeding mesenchymal stromal cells (MSCs) on engineered hydrogels mimicking soft tissue elasticity leads to an approximately 10-fold increase in extracellular vesicles (EVs) secretion per cell, potentially due to faster transport of multivesicular bodies (MVBs) within MSCs on soft hydrogels, resulting in increased EV secretion. The study also revealed that the Actin-related protein 2/3 complex, rather than myosin-II, limits MVB transport and EV secretion from MSCs on hydrogels.
Article
Biochemistry & Molecular Biology
Elia Bari, Fulvio Tartara, Fabio Cofano, Giuseppe di Perna, Diego Garbossa, Sara Perteghella, Marzio Sorlini, Delia Mandracchia, Lorella Giovannelli, Paolo Gaetani, Maria Luisa Torre, Lorena Segale
Summary: The study found that the mesenchymal stem cell-secretome Lyosecretome has a significant improvement effect on the osteoinductive and osteoconductive properties of titanium cages, leading to increased mineralized matrix when used during culturing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Cristiana Ulpiano, Claudia L. da Silva, Gabriel A. Monteiro
Summary: Extracellular vesicles (EVs) are cell-derived lipid membranous structures that modulate cell-cell communication and have potential as drug delivery vehicles. Mesenchymal stromal cells (MSCs) secrete EVs which can be bioengineered to enhance their therapeutic potential. This review covers the fundamentals of EV biology, bioengineering strategies, and applications of bioengineered MSC-EVs, as well as the technical challenges to their clinical translation.
Article
Engineering, Biomedical
Ye Li, Yin-Hsueh Chen, Bing-Yun Liu, Qing Nie, Li-Jun Li, Xu Duan, Lian-Zhi Wu, Gang Chen
Summary: This study investigates the heterogeneity of mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) harvested from different tissues. It finds that there is no difference in the basic parameters, stability, and biosafety of different MSC-EVs. However, umbilical cord stem/stromal cell (UCSC) EVs and dental pulp stem/stromal cell (DPSC) EVs demonstrate better drug loading/delivery capacity. The heterogeneity of different MSC-EVs in cargo diversity, cellular affinity, organ biodistribution, and therapeutic effects may guide the rational selection in different disease treatments. A combined assessment provides a rational strategy for selecting MSC-EVs in future clinics.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Cell & Tissue Engineering
Davod Pashoutan Sarvar, Hosein Effatpanah, Parvin Akbarzadehlaleh, Karim Shamsasenjan
Summary: The study highlights the important role of MSC-derived extracellular vesicles (MSC-EVs) in hematopoietic regulation and immune response after transplantation. MSC-EVs directly fuse with hematopoietic stem cell membranes, affecting their fate, and regulate the proliferation and differentiation of hematopoietic stem cells through the release of various bioactive factors.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Peripheral Vascular Disease
Alfonso Eirin, Lilach O. Lerman
Summary: MSC-derived extracellular vesicles (EVs) have the potential to modulate pathways responsible for renal injury, including inflammation, oxidative stress, apoptosis, fibrosis, and microvascular remodeling, leading to renoprotective effects in experimental studies. However, scarce clinical data and challenges such as standardization of methods for EV isolation and characterization, EV fate, duration of EV effects, and effects of cardiovascular risk factors need to be addressed for successful clinical translation.
Article
Orthopedics
Nobutake Ozeki, Hideyuki Koga, Junpei Matsuda, Yuji Kohno, Mitsuru Mizuno, Hisako Katano, Kunikazu Tsuji, Tomoyuki Saito, Takeshi Muneta, Ichiro Sekiya
JOURNAL OF ORTHOPAEDIC SCIENCE
(2020)
Article
Orthopedics
Hiroaki Onuma, Kunikazu Tsuji, Takashi Hoshino, Kei Inomata, Mio Udo, Yusuke Nakagawa, Hiroki Katagiri, Kazumasa Miyatake, Toshifumi Watanabe, Ichiro Sekiya, Takeshi Muneta, Hideyuki Koga
JOURNAL OF ORTHOPAEDIC RESEARCH
(2020)
Article
Orthopedics
Hiroko Ueki, Hiroki Katagiri, Kunikazu Tsuji, Kazumasa Miyatake, Toshifumi Watanabe, Ichiro Sekiya, Takeshi Muneta, Hideyuki Koga
Summary: The study found that an appropriate number of MSCs in the rat model can reduce articular cartilage degeneration and decrease pain levels, while increasing the number of cells further protects the articular cartilage from degeneration.
JOURNAL OF ORTHOPAEDIC SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Aidehamu Aihemaiti, Naoki Yamamoto, Jinying Piao, Takuya Oyaizu, Hiroki Ochi, Shingo Sato, Atsushi Okawa, Toshio Miyata, Kunikazu Tsuji, Yoichi Ezura, Yoshinori Asou
Summary: The novel orally available PAI-1 inhibitor TM5484 shows promising potential in preventing sarcopenia by enhancing calf muscle force and improving muscle fiber thickness. Treatment with TM5484 increases the expression of key genes in mouse muscle, and also exerts a positive cell autonomous effect.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Orthopedics
J-S An, K. Tsuji, H. Onuma, N. Araya, M. Isono, T. Hoshino, K. Inomata, J. Hino, M. Miyazato, H. Hosoda, K. Kangawa, Y. Nakagawa, H. Katagiri, K. Miyatake, I Sekiya, T. Muneta, H. Koga
Summary: This study demonstrated that C-type natriuretic peptides (CNP) inhibited fibrotic changes in the infrapatellar fat pad (IFP) after acute joint inflammation, alleviating persistent pain and significantly improving articular cartilage degeneration.
OSTEOARTHRITIS AND CARTILAGE
(2021)
Letter
Orthopedics
Kunikazu Tsuji
JOURNAL OF ORTHOPAEDIC RESEARCH
(2021)
Article
Multidisciplinary Sciences
Kiyotaka Horiuchi, Nobutake Ozeki, Kentaro Endo, Mitsuru Mizuno, Hisako Katano, Masako Akiyama, Kunikazu Tsuji, Hideyuki Koga, Ichiro Sekiya
Summary: The study demonstrates that thawed MSCs show comparable inhibitory effects on OA progression in rats to cultured MSCs. Additionally, in the rat OA model, the thawed MSC group had significantly lower gross finding and histological scores compared to the cryopreservation fluid group.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Guo Tang, Yoshinori Asou, Etsuko Matsumura, Yusuke Nakagawa, Kazumasa Miyatake, Hiroki Katagiri, Tomomasa Nakamura, Hideyuki Koga, Keiichiro Komori, Ichiro Sekiya, Yoich Ezura, Kunikazu Tsuji
Summary: IL1β enhances the proliferation of synovial mesenchymal stem/stromal cells through intracellular IL1 receptor IL1R1/CD121a, and the growth-promoting effect of IL1β can be separated from its function of inducing inflammatory cytokines in the cells.
Article
Multidisciplinary Sciences
Masaaki Isono, Jun Takeuchi, Ami Maehara, Yusuke Nakagawa, Hiroki Katagiri, Kazumasa Miyatake, Ichiro Sekiya, Hideyuki Koga, Yoshinori Asou, Kunikazu Tsuji
Summary: Fibroblastic cells from synovial membrane in knee joint can give rise to MSC-like cells in culture, and the CD44 signaling pathway plays an important role in the formation and maintenance of MSCs.
Article
Orthopedics
Zhen Qu, Hideyuki Koga, Kunikazu Tsuji, Guo Tang, Yang Yang, Aritoshi Yoshihara, Mai Katakura, Hiroki Katagiri, Kazumasa Miyatake, Tomomasa Nakamura, Ichiro Sekiya, Yusuke Nakagawa
Summary: In this study, the effects of hyaluronic acid (HA) sheet transplantation on infrapatellar fat pad (IFP) fibrosis and articular cartilage degeneration were examined in a rat arthritis model. Results showed that HA sheets could alleviate persistent pain, inhibit articular cartilage degeneration, and suppress fibrosis and nerve fiber invasion in the IFP. The HA sheets remained histologically until 10 days after transplantation.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2023)
Article
Neurosciences
Leyang Li, Su Chen, Hiroyuki Yokoyama, Hidetoshi Kaburagi, Takashi Hirai, Kunikazu Tsuji, Mitsuhiro Enomoto, Yoshiaki Wakabayashi, Atsushi Okawa
Summary: Peripheral nerve injury (PNI) leads to severe functional loss in extremities, and delayed nerve repair results in muscle denervation and atrophy. To better understand NMJ degeneration and regeneration after PNI, we established two models of nerve repair in mice and compared their outcomes. Our results suggest that allogeneic nerve grafting is more effective than end-to-end neurorrhaphy in promoting functional recovery and increasing reinnervated NMJs and Schwann cells in the target muscle. Further investigation is needed to explore the relationship between NMJ and Schwann cells in the target muscle.
Article
Biochemistry & Molecular Biology
Hiroki Katagiri, Kaori Nakamura, Takeshi Muneta, Toshifumi Watanabe, Kazumasa Miyatake, Ichiro Sekiya, Hideyuki Koga, Kunikazu Tsuji
Summary: The study revealed changes in synovial fluid cell population and their relationship with postoperative pain after ACLR. The granulocyte population in synovial fluid negatively correlated with postoperative pain 4 weeks after surgery and was associated with levels of IL1 beta and IL8. An increase in met-enkephalin concentration at 4 days post-surgery tended to reduce pain at rest.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2021)
Meeting Abstract
Orthopedics
K. Kawata, H. Katagiri, K. Tsuji, K. Miyatake, Y. Nakagawa, I. Sekiya, H. Koga
OSTEOARTHRITIS AND CARTILAGE
(2021)
Article
Cell Biology
Leyang Li, Hiroyuki oYokyama, Hidetoshi Kaburagi, Takashi Hirai, Kunikazu Tsuji, Mitsuhiro Enomoto, Yoshiaki Wakabayashi, Atsushi Okawa
NEURAL REGENERATION RESEARCH
(2020)